PNAS Plus Significance Statements
2013
Proceedings of the National Academy of Sciences of the United States of America
Ribosomes synthesize all proteins in living cells. There are limits, however, to which sequences they can make. We identified (pp. E878-E887) short motifs within translating proteins that inhibit their own synthesis. We developed in vitro methods to determine the molecular mechanism of ribosome stalling by these motifs. Some act by blocking the formation of peptide bonds; in a few of these cases, a translation factor, elongation factor P, alleviates stalling. Other motifs block release of the
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... otein at stop codons. Stalling motifs occur less often than expected in bacterial proteins, suggesting that proteins have evolved to be synthesized efficiently. Early immune response has to discriminate a few foreign peptides rapidly from a vast excess of self-peptides, and it is unclear in quantitative terms how this is possible. We show (pp. E888-E897) that a generic proofreading cascade supplemented by a single negative feedback mediated by the Src homology 2 domain phosphatase-1 (SHP-1) accounts quantitatively for this discrimination. Our model, with minimal variables and parameters, can fit a large body of experimental data and accounts for phenotypes in T-cell activation. New experiments validate our predictions and provide a quantitative understanding of antagonism, the effect by which foreign ligands close to activation alter the immune response. In mammals, hair follicles reside in the skin together with a set of follicle-associated structures: sebaceous glands, nerve fibers, specialized sensory cells, and muscle fibers. In general, the follicle and its associated structures are precisely oriented with respect to the body axes. The present study (pp. E908-E917) shows that, in mice genetically engineered to lack the follicle orienting system, the follicleassociated structures-with the exception of the specialized sensory cells-acquire an orientation that matches that of the follicle. These experiments imply that hair follicles communicate local orienting information to most of their associated structures. Wnt and CDK-1 regulate cortical release of WRM-1/β-catenin to control cell division orientation in early Caenorhabditis elegans embryos
doi:10.1073/pnas.ss11010
fatcat:pf5ncmww5vapllsxjbcvtcyodq